a phase i, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of hiv-1 mn rsgp120 and bivalent aidsvax b/e (hiv-1 mn rgp120/a244 rgp120) in combination with qs-21 with or without alum in healthy hiv-1 uninfected adults

Conditions: HIV Infections

Summary: to assess the safety and immune response to two experimental vaccines when formulated with qs-21 or qs-21 plus alum. to determine whether the new preparation of qs-21 in polysorbate 80 is less reactogenic than the qs-21 formulation used in aveg protocols 016, 016a, and 016b. to examine whether qs-21 is immunologically equivalent to that used in 16b. to determine if qs-21, when given with low doses of antigen, induces measurable hiv-1-specific ctl activity. to evaluate if the qs-21 dose-sparing effect extends to an antigen dose of 0.5 micrograms. to determine if the bivalent vaccine gives responses equivalent to the monovalent product or if a broadening of the hiv-1-specific binding and neutralizing antibody responses occurs. an effective vaccine to prevent hiv-1 infection may need to generate diverse and multifaceted immunologic responses. required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of hiv-1; t cell help provided by both cd4 and cd8 positive subsets; and a class i-restricted cytotoxic lymphocyte response. other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible.

an effective vaccine to prevent hiv-1 infection may need to generate diverse and multifaceted immunologic responses. required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of hiv-1; t cell help provided by both cd4 and cd8 positive subsets; and a class i-restricted cytotoxic lymphocyte response. other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible. volunteers in each of 5 groups receive vaccine or placebo by intramuscular injection at months 0, 1, and 6. all patients receive one of two doses of qs-21 along with vaccine or placebo and some groups receive alum as follows: group 1: low-dose mn rsgp120/hiv-1 plus qs-21 (13 volunteers). group 2: high-dose mn rsgp120/hiv-1 plus qs-21 (13 volunteers). group 3: aidsvax b/e (injection contains each of the two vaccine components, hiv-1 mn rgp120 and a244 rgp120/hiv-1) plus qs-21 plus alum (13 volunteers). group 4: high-dose mn rgp120/hiv-1 plus qs-21 plus alum (13 volunteers). group 5: placebo plus qs-21 (8 volunteers). volunteers will be closely monitored after each immunization and followed for a minimum of 12 months after the initial immunization.

Eligibility criteria:
inclusion criteria volunteers must have: * negative elisa for hiv within 8 weeks prior to immunization. * cd4 count greater than or equal to 400 cells/mm3. * normal history and physical examination. \[refer to laboratory values for additional requirements.\] exclusion criteria co-existing condition: volunteers with the following conditions or symptoms are excluded: * medical or psychiatric conditions or occupational responsibilities which preclude subject compliance with the protocol. * recent suicidal ideation or psychosis. * active syphilis. note: if the serology is documented to be a false positive or due to a remote (greater than 6 months) treated infection, the volunteer is eligible. * active tuberculosis. note: volunteers with a positive ppd and a normal chest x-ray showing no evidence of tb and not requiring inh therapy are eligible. * positive for hepatitis b surface antigen. volunteers with the following prior conditions are excluded: * history of immunodeficiency, chronic illness, or autoimmune disease. * history of cancer unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure. * history of suicide attempts, recent suicidal ideation, or past or present psychosis. * history of anaphylaxis or other serious adverse reactions to vaccines. * history of serious allergic reaction to any substance requiring hospitalization or emergency medical care (e.g., stevens-johnson syndrome, bronchospasm, or hypotension). * history of reaction to thimerosal. prior medication: excluded: * live attenuated vaccine within 60 days of study. note: medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away from hiv immunizations. * experimental agents within 30 days prior to study. * hiv-1 vaccines or placebo as part of a previous hiv vaccine trial. prior treatment: excluded: * blood products or immunoglobulin in the past 6 months. * experimental agents within 30 days prior to study. risk behavior: excluded: * volunteers with an identifiable higher- or intermediate-risk sexual behavior for hiv infection (i.e., aveg risk groups c or d ). * history of intravenous drug use within 12 months prior to enrollment.

Keywords: vaccines, synthetic hiv antibodies hiv antigens hiv-1 adjuvants, immunologic aids vaccines t-lymphocytes, cytotoxic hiv seronegativity hiv envelope protein gp120 alum compounds hiv preventive vaccine